Chemotherapeutic properties and side-effects associated with the clinical practice of terpene alkaloids: paclitaxel, docetaxel, and cabazitaxel

Abstract

Over the years, many biological and synthetic agents have been explored and tested in attempts to halt the spread of cancer and/or cure it. Currently, several natural compounds have and are being considered in this regard. For example, paclitaxel is a potent anticancer drug that originates from the tree Taxus brevifolia. Paclitaxel has several derivatives, namely, docetaxel and cabazitaxel. These agents work by disrupting microtubule assembling dynamics and inducing cell cycle arrest at the G2/M phase of the cell cycle, ultimately triggering apoptosis. Such features have helped to establish paclitaxel as an authoritative therapeutic compound against neoplastic disorders. After the completion of compound (hemi) synthesis, this drug received approval for the treatment of solid tumors either alone or in combination with other agents. In this review, we explore the mechanisms of action of paclitaxel and its derivatives, the different formulations available, as well as the molecular pathways of cancer resistance, potential risks, and other therapeutic applications. In addition, the role of paclitaxel in hematological malignancies is explored, and potential limitations in the therapeutic use of paclitaxel at the clinical level are examined. Furthermore, paclitaxel is known to cause increased antigen presentation. The immunomodulatory potential of taxanes, alone or in combination with other pharmacologic agents, is explored. Despite terpene-alkaloids derivatives’ anti-mitotic potential, the impact of this class of drugs on other oncogenic pathways, such as epithelial-to-mesenchymal transition and the epigenetic modulation of the transcription profile of cancer cells, is also analyzed, shedding light on potential future chemotherapeutic approaches to cancer.

Glycopolymeric Photoactive Micelles for Glucose Transporter-Targeted Synergistic Combination Therapy

“…The mechanism of interaction between PTX-loaded GPMs and PDT treatment was examined by cell cycle assay with or without light irradiation (Figures B, S15). It has been reported that a high concentration of PTX causes mitotic arrest at the G2/M phase, whereas a low concentration of PTX induces apoptosis and causes arrest at the G0/G1 phase . GPM1–PTX and GPM2–PTX at low concentration caused G0/G1 phase arresting, both in the absence and presence of light irradiation.…”

“…It has been reported that a high concentration of PTX causes mitotic arrest at the G2/M phase, whereas a low concentration of PTX induces apoptosis and causes arrest at the G0/G1 phase. 59 GPM1−PTX and GPM2−PTX at low concentration caused G0/G1 phase arresting, both in the absence and presence of light irradiation. However, free PTX caused G0/ G1 phase arrest without NIR irradiation whereas subG1 populations increased in free PTX groups with NIR irradiation.…”

Durvalumab and taxane family combination therapy enhances the antitumoral effects for NSCLC: An in vitro study

“…Although the effect of the taxane family on cell migration and invasiveness of ovary cancer cells, umbilical vein endothelial cells, and glioma cells has been described, the DVL effect on cell migration has not been evaluated. 26 Besides these, real-time PCR results show that combination therapy with these agents increased the expression level of the proand antiapoptotic genes (Bax, Bcl-2, P53, Cas-3), compared to monotherapy. Also, the combination of PTX/DVL and DTX/DVL enhanced the expression level of Cas-3 and p53 as compared to DVL alone.…”

Network pharmacology and experimental verification reveal the mechanism of safranal against glioblastoma (GBM)

“…Researchers are using scientific approaches to elucidate their mechanisms, safety and efficacy ( 40 ). For example, paclitaxel is a potent anticancer drug that originates from the tree Taxus brevifolia ( 41 ); β-Elemene is a sesquiterpene compound extracted from the herb Curcuma Rhizoma, which is used to treat several types of cancer with no reported severe adverse effects ( 42 ).…”